There has been a tremendous surge in the number of ultrasound guided transperineal prostate implants performed in recent years. Effective implants require involved treatment planning based on three-dimensional multi-modality (magnetic resonance imaging, ultrasound, computed tomography) images used in combination with one another. A multi-modality prostate imaging phantom could have applications in quality assurance, image registration and treatment planning. Three human soft tissues relevant to a prostate phantom that should be mimicked for magnetic resonance imaging (MRI), ultrasound, and computed tomography (CT) are prostate parenchyma, skeletal muscle and adipose (fat) tissue.
Tissue-mimicking (TM) materials must exhibit the same properties relevant to a particular imaging modality as actual human soft tissues. Tissue-mimicking materials for use in magnetic resonance imaging phantoms should have values of characteristic relaxation times, T1 and T2, which correspond to those of the tissue represented at the Larmor frequency of concern. Soft tissues exhibit T1 values ranging from about 200-1200 ms and T2 values from about 40-200 ms. For given soft tissue, T1 in particular can exhibit a significant dependence on frequency as well as on temperature. However, for multi-modality imaging phantoms, in general, measurements may be performed near the available clinical Larmor frequency of an MRI system (typically 64 MHz or 85 MHz) and at room temperature. Phantoms must be assumed to be useful at room temperature even though their properties must mimic those of soft tissues at the normal body temperature of 37.degree. C.
The ideal tissue-mimicking material for use in ultrasound should have the same ranges of speeds of sound, attenuation coefficients, and backscatter coefficients as soft tissue. These parameters should be controllable in the manufacturing process of the phantom material, and their variation within the range of room temperatures should be small. Speeds of sound in human soft tissues vary over a fairly small range with an average value of about 1540 m/s. The speed of sound in fat is thought to be about 1470 m/s. The amplitude attenuation coefficients appear to vary over the range from 0.4 dB/cm to about 2 dB/cm at a frequency of 1 MHz in these tissues. The frequency dependencies of the attenuation coefficient of some soft tissues have been studied and, typically, it has been reported that the attenuation coefficient is approximately proportional to the ultrasonic frequency in the diagnostic frequency range of 1 to 10 MHz. An exception is breast fat, in which the attenuation coefficient is proportional to the frequency to the 1.7 power.
F. T. D'Astous and F. S. Foster, "Frequency Dependence of Attenuation and Backscatter in Breast Tissue," Ultrasound in Med. & Biol., Vol. 12, pp. 795-808 (1986).
For use in computed tomography (CT), the tissue-mimicking materials must exhibit the same CT number as that of the tissue being mimicked. The CT numbers for most soft tissues lie in the range of about 20-70 at the typical effective x-ray energy of a clinical CT scanner except for fat where the CT number is about -100.
In addition to the individual imaging modality parameters listed above, tissue-mimicking materials must also exhibit long term stability and ease of storage without which they are rendered useless in an imaging phantom.
An ultrasound phantom containing tissue-mimicking material is disclosed in U.S. Pat. No. 4,277,367, to Madsen, et al., entitled Phantom Material and Methods, in which both the speed of sound and the ultrasonic attenuation properties could be simultaneously controlled in a mimicking material based on water based gels, such as those derived from animal hides. In one embodiment, ultrasound phantoms embodying the desired features for mimicking soft tissue were prepared from a mixture of gelatin, water, n-propanol and graphite powder, with a preservative. In another embodiment, an oil and gelatin mixture formed the basis of the tissue-mimicking material.
Tissue-mimicking material is typically used to form the body of an ultrasound scanner phantom. This is accomplished by enclosing the material in a container which is closed by an ultrasound transmitting window cover. The tissue-mimicking material is admitted to the container in such a way as to exclude air bubbles from forming in the container. Tissue-mimicking materials may contain scattering particles, spaced sufficiently close to each other that an ultrasound scanner is incapable of resolving individual scattering particles. Testing spheres of tissue-mimicking material, or other targets, may be located within the phantom container, suspended in the tissue-mimicking material body. The objective is for the ultrasound scanner to resolve the testing spheres or other targets from the background material and scattering particles. This type of ultrasound phantom is described in U.S. Pat. No. 4,843,866, to Madsen, et al., entitled Ultrasound Phantom.
U.S. Pat. No. 5,625,137 to Madsen, et al. discloses a tissue-mimicking material for ultrasound phantoms with very low acoustic backscatter coefficient that may be in liquid or solid form. A component in both the liquid and solid forms is a filtered aqueous mixture of large organic water soluble molecules and an emulsion of fatty acid esters, which may be based on a combination of milk and water. Hydroxy compounds, such as n-propanol, can be used to control the ultrasonic speed of propagation through the material and a preservative from bacterial invasion can also be included. The use of scattering particles allows a very broad range of relative backscatter levels to be achieved.
Hydrogen magnetic resonance imaging (MRI) (also known as nuclear magnetic resonance, or NMR, imaging) is generally a more complicated imaging procedure than X-ray or ultrasound since it does not measure just one dominant property, such as electron density in the case of X-ray computed tomography, but is affected by the hydrogen atom density, flow, and two relaxation phenomena. The contrast, or differences in image brightness, in an MRI image is primarily due to differences in the relaxation times of tissues. It has been found that there are relaxation time differences between normal tissue and certain tumors, which makes MRI imaging potentially very valuable in early detection of such tumors.
A satisfactory MRI phantom must satisfy several requirements. First, the material of which the phantom is made should mimic the hydrogen density and relaxation times of several types of tissues. Second, the relaxation times of the material should not change over time, such as over several months or years, so that the phantom can be used in tests of imager reproducibility. Third, if the phantom includes inclusions of materials within the surrounding matrix which have different NMR characteristics than the surrounding matrix, these inclusions must be stable over time in both shape and in NMR relaxation times, T1 and T2.
Soft tissues exhibit T2's from about 40 ms to 200 ms. Typical values for the ratio T1/T2 lie between 4 and 10 for soft tissues. For a given soft tissue parenchyma, T1 in particular can exhibit a significant dependence on frequency as well as temperature.
Materials which have been proposed for use in phantoms to mimic soft tissues with respect to one or more NMR properties include aqueous solutions of paramagnetic salts and water based gels of various forms. Such gels may also contain additives such as a paramagnetic salt for control of T1. Aqueous solutions of paramagnetic salts can be used in phantoms to produce a desired value of either T1 or T2. The ratio of T1/T2 in the salt solutions is almost always less than 2, however, rendering such solutions inadequate for the close mimicking of soft tissue, with the possible exception of body fluids.
Phantom materials composed of water based agar gels doped with MnCl.sub.2 to control T1 have been reported. R. Mathur-DeVre, et al., "The Use of Agar as a Basic Reference for Calibrating Relaxation Times and Imaging Parameters," Magn. Reson. Med., Vol. 2, 1985, p. 176. Agar gels doped with CuSO.sub.4 have also been reported. M. D. Mitchell, et al., "Agarose as a Tissue-Equivalent Phantom Material for NMR Imaging," Magn. Reson. Imag., Vol. 4, 1986, p. 263.
A phantom material consisting of mixtures of agar gel and animal hide gel in which CuSO.sub.4 was used to lower T1 has also been reported. Unfortunately, a long-term instability manifested itself in that a steady, very slow rise in T1 was observed over a period of months. This instability precludes the use of this material in MRI phantoms. The rise in T.sub.1 was perhaps due to the slow formation of metal-organic complexes, removing the Cu.sup.++ paramagnetic ions. J. C. Blechinger, et al., "NMR Properties for Tissue-Like Gel Mixtures for Use as Reference Standards or in Phantoms," Med. Phys., Vol. 12, 1985, p. 516 (Abstract).
More recently, the problem of gradual increase in T1 in the agar, animal hide gel, Cu.sup.++ SO.sub.4.sup.- gel has been eliminated by addition of the chelating agent EDTA (ethylenediaminetetraacetic acid). This stable material is excellent for use in MRI phantoms. See J. R. Rice, et al., "Anthropomorphic .sup.1 H MRS Head Phantom," Medical Physics, Vol. 25, 1998, pp. 1145-1156.
U.S. Pat. No. 5,312,755 to Madsen et al. discloses a tissue-mimicking NMR phantom that utilizes a base tissue-mimicking material which is a gel solidified from a mixture of animal hide gelatin, agar, water and glycerol. The amount of glycerol could be used to control the T1. The preferred base material included a mixture of agar, animal hide gelatin, distilled water (preferably deionized), glycerol, n-propyl alcohol, formaldehyde, and p-methylbenzoic acid. The contrast resolution phantom could include inclusions which have NMR properties which differ from the base tissue-mimicking material. Differences in contrast between the surrounding base material and the spherical inclusions could also be obtained by the use of a solid such as powdered nylon added to the base material and the inclusions that has little NMR response but displaces some of the gelatin solution, decreasing the apparent .sup.1 H density to the NMR instrument.
As noted above, phantoms for use in MRI systems made from water-based agarose gels along with a copper salt have been made previously. M. D. Mitchell, et al., supra. The T1 and T2 relaxation rates are strongly dependent on the concentrations of agarose and copper ions in the tissue-mimicking sample with the T1 depending more on the copper and the T2 depending more strongly on the concentration of dry weight agarose in the sample. Burlew et al. "A New Ultrasound Tissue-Equivalent Material," Radiology, Vol. 134, 1980, pp. 517-520, have described a polysaccharide gel (agar) for ultrasound phantoms that can be made to exhibit speeds of sound over the range of 1498 m/s to 1600 m/s at 22.degree. C.
A prostate phantom based on CT slices and made from solid water (Gammex/RMI, Madison, Wis.) for imaging, volume rendering, treatment planning, and dosimetry applications has also been constructed. B. B. Paliwal, et al., "A Solid Water Pelvic and Prostate Phantom for Imaging, Volume Rendering, Treatment Planning, and Dosimetry for an RTOG Multi-Institutional, 3-D Dose Escalation Study," International Journal of Radiation Oncology, Biology, Physics, Vol. 42, 1998, pp. 205-211.
An earlier investigation had reported on whether tissue-mimicking (TM) materials for ultrasound might be appropriate for use in magnetic resonance imaging (MRI) phantoms as well. See, E. L. Madsen, et al., "Prospective Tissue-mimicking Material For Use In NMR Imaging Phantoms," Magn. Reson. Imaging, Vol. 1, 1982, pp. 135-141. These materials consisted of powdered graphite and preservatives in water-based proteinaceaous gels. Though the materials looked promising initially, later measurements revealed that, although T1 was mimicked adequately, it was the T2* which was being controlled through concentration of graphite, not T2 itself. For tissue-mimicking materials, it is the T2 which must be controlled because T2 is intrinsic to the material whereas T2* is influenced by the involved imager instrumentation.